（外文）2017更新异常子宫出血的管理-main（下）

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%1 in another [57]. Regarding satisfaction, results are identical at

%1 2 years follow-up [51,57].

%1 More minor side effects are described for the IUS (spotting

%1 mainly). However,  in  terms of  strategy of  cost-effectiveness,

%1 treatment with IUS appears more favorable [51].

%1 Compared with hysterectomy, Levonorgestrel-releasing intra-

%1 uterine system is less effective on bleeding. In terms of quality of

%1 life, they would be equivalent at 5 to 10 years follow-up, but after

%1 10 years, nearly 50% of women who initially received IUS have had

%1 a hysterectomy [51,57]. Regarding the treatment strategy, two

%1 literature reviews [51,58] found different results, one in favor of

%1 the Levonorgestrel-releasing intrauterine system and one in favor

%1 of hysterectomy.

%1 Combined hormonal contraceptives. The use of combined contra-

%1 ception in cases of uterine bleeding without anatomical focal

%1 lesion (submucosal myoma, polyp, endometrial cancer) is possible.

%1 It has been used for a long time. Its action is based on inhibition of

%1 the hypothalamic-pituitary axis and endometrial atrophy.

%1 However, many women in the age groups suffering from AUB

%1 have relative or absolute contraindication to their use.

%1 The efficacy has been shown, with a reduction of bleeding

%1 volume  ranging  from  35  to  69%  [59].  It  is  less  than  the

%1 Levonorgestrel-releasing intrauterine system [51,59], and more

%1 than progestins in luteal phase, NSAIDs and tranexamic acid

%1 [59].

%1 Some combined oral contraceptive pills have been specifically

%1 studied in this indication, as well as other routes of administration

%1 (oral, transdermal, vaginal). Whatever the mode of administration,

%1 prolonged use reduces the number of bleeding episodes and the

%1 amount of bleeding per cycle [60,61] according to most studies.

%1 The prescription must respect the contraindications of the oral

%1 pills.

%1 Oral progestins. Their action is based on the endometrial atrophy.

%1 Therefore, their primary use is limited to patients with endometrial

%1 hypertrophy and willing to preserve their fertility.

%1 Oral intake of progestins may follow two regimens: luteal phase

%1 intake, for 10 to 14 days per cycle, or prolonged intake, for 21 days

%1 per cycle. Luteal phase regimen does not appear to improve

%1 abnormal bleeding, except in the case of anovulatory bleeding

%1 [55,62].  In  contrast,  prolonged  regimen  is  responsible  for  a

%1 significant reduction of functional bleeding regardless of etiology

%1 [62]. Nevertheless, the effectiveness on bleeding is lower than that

%1 of Levonorgestrel-releasing intrauterine system [55] with side

%1 effects considered less acceptable.

%1 Injectable progesterone, if it allows amenorrhea in approxi-

%1 mately 50% of women at 1 year [63] has not been studied in this

%1 indication.

%1 GnRH Agonists. Their action is based on inhibition of the gonadal

%1 axis, responsible for hypogonadism with endometrial atrophy and

%1 secondary amenorrhea. There is also a specific effect on the

%1 decrease in volume of potential myomas.

%1 Because of significant side effects in the short and long term,

%1 their use is reserved for preoperative management of myomas. The

%1 myoma volume reduction is significant, up to 60% [64].

%1 Prolonged use beyond 6 months must be accompanied by

%1 additional hormonal combined treatment which may alter the

%1 effectiveness of treatment on abnormal bleeding and the volume of

%1 myomas [65].

%1 Ulipristal  Acetate  (Esmya1). Ulipristal  acetate  is  a  selective

%1 modulator of progesterone receptor (SPRM). It displays a partial

%1 antagonistic effect on myomatous tissue [66,67]. It induces cellular

%1 apoptosis,  inhibits  cell  proliferation  and  neoangiogenesis  in

myomas. There is a reduction of about 25% in the size of myomas	455
in 80% of women after a course of 3 months of treatment, and 50%	456
after two courses of three months for 50% of women. It achieves	457
amenorrhea rates greater than 80% [68].	458
Since February 2012, ulipristal acetate is authorized in Europe	459
as preoperative management of myomas. Regimen includes up to	460
4 courses of treatment in sequential therapy, each sequence lasting	461
3 months. Its use changes the surgical approach route (via a	462
decrease  in  volume  of  myomas).  It  helps  restore  normal	463
hemoglobin  preoperatively.  In  some  cases,  surgery  may  be	464
unnecessary after the treatment [69].	465
Since May 2015 ulipristal acetate is also indicated as sequential	466
treatment for moderate to severe symptoms of uterine myomas.	467
Special case: high-dose estrogens in acute heavy bleeding. The use of	468
high-dose intravenous estrogen is quickly effective on uterine	469
bleeding but this treatment is seldom proposed in clinical practice	470
[70].	471
Non-hormonal treatments	472
NSAID. NSAIDs have a mixed effect on reducing bleeding and	473
dysmenorrhea. Their use is contraindicated, among other, in case	474
of allergy, gastritis and peptic ulcer disease.	475
NSAIDs provide a 33 to 55% reduction of the volume of	476
menstruations compared to placebo. However, their effectiveness	477
is lower than that of Levonorgestrel-releasing intrauterine system	478
and tranexamic acid, and is equivalent to that of combined	479
contraceptives and progestins in luteal phase [53].	480
Their use is restricted to bleeding episodes. Studies do not favor	481
a particular NSAID.	482
Tranexamic acid. Tranexamic acid is an antifibrinolytic agent that	483
has shown efficacy against placebo with a reduction in menstrual	484
blood loss of 34 to 59% [54,71,72].	485
Literature reviews show superior efficacy of tranexamic acid	486
over progestins in luteal phase and NSAIDs. However, it is less	487
efficient than the Levonorgestrel-releasing intrauterine system	488
[54,72].	489
Tranexamic  acid  is  responsible  for  very  few  side  effects	490
(equivalent to placebo and patients’ satisfaction is good, around	491
80% [72].	492
The risk of thromboembolic events during treatment with	493
tranexamic acid is not higher than in the general population, even	494
in women with risk factors [54,72,73].	495
As for NSAIDs, treatment should only be prescribed for bleeding	496
phases only. It is not a preventive treatment.	497
Treatment of the anemia. Treatment by iron supplementation is	498
indicated in case of iron deficiency anemia.	499
The correction of anemia is particularly important preopera-	500
tively. Indeed, there is a significant increase in morbidity and	501
mortality in the case of uncorrected anemia [74].	502
Surgical treatment	503
Most scientific societies do not recommend surgery as a first-	504
line treatment [4,6,13,14], except when endometrial lesions may	505
contribute to bleeding (myoma, polyp, endometrial hyperplasia).	506
Conservative treatment should however be considered in case	507
of ineffective medical treatment or when it is contraindicated.	508
Surgical alternatives should however be offered only to women	509
who no longer desire pregnancy or in absence of myoma type 0,1.	510
Endometrial  destruction  is  associated  with  subfertility,  and	511
pregnancies described in this context are marked by frequent	512
and  severe  obstetric  complications  (pregnancy  loss,  ectopic	513
pregnancies, abnormal placentation, hemorrhage. . .) [75].	514

Please cite this article in press as: Levy-Zauberman Y, et al. Update on the management of abnormal uterine bleeding. J Gynecol Obstet Hum Reprod (2017), http://dx.doi.org/10.1016/j.jogoh.2017.07.005

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8Y. Levy-Zauberman et al. / J Gynecol Obstet Hum Reprod xxx (2017) xxx–xxx

Fig. 4. Patient with further pregnancy project.

Fig. 5. Patient without further pregnancy project.

Please cite this article in press as: Levy-Zauberman Y, et al. Update on the management of abnormal uterine bleeding. J Gynecol Obstet Hum Reprod (2017), https://wwwrcogorguk/globalassets/

%1 http://wwwcancerresearchukorg/health-professional/

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	http://dx.doi.org/10.1016/j.jogoh.2017.07.005

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Please cite this article in press as: Levy-Zauberman Y, et al. Update on the management of abnormal uterine bleeding. J Gynecol Obstet Hum Reprod (2017), http://dx.doi.org/10.1016/j.jogoh.2017.07.005

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